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Pioglitazone use and risk of bladder cancer: population based cohort study

BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i1541 (Published 30 March 2016) Cite this as: BMJ 2016;352:i1541
  1. Marco Tuccori, postdoctoral fellow1 2,
  2. Kristian B Filion, assistant professor of medicine1 2 3,
  3. Hui Yin, statistician1,
  4. Oriana H Yu, endocrinologist1 4,
  5. Robert W Platt, professor of biostatistics1 2 5 6,
  6. Laurent Azoulay, associate professor of oncology1 7
  1. 1Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
  2. 2Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal
  3. 3Division of Clinical Epidemiology, McGill University
  4. 4Division of Endocrinology, Jewish General Hospital, Montreal
  5. 5Department of Pediatrics, McGill University, Montreal
  6. 6Research Institute of the McGill University Health Centre, Montreal
  7. 7Department of Oncology, McGill University
  1. Correspondence to: L Azoulay laurent.azoulay{at}mcgill.ca
  • Accepted 29 February 2016

Abstract

Objective To determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.

Design Population based cohort study.

Setting General practices contributing data to the United Kingdom Clinical Practice Research Datalink.

Participants A cohort of 145 806 patients newly treated with antidiabetic drugs between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014.

Main outcome measures The use of pioglitazone was treated as a time varying variable, with use lagged by one year for latency purposes. Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident bladder cancer associated with pioglitazone overall and by both cumulative duration of use and cumulative dose. Similar analyses were conducted for rosiglitazone, a thiazolidinedione not previously associated with an increased risk of bladder cancer.

Results The cohort generated 689 616 person years of follow-up, during which 622 patients were newly diagnosed as having bladder cancer (crude incidence 90.2 per 100 000 person years). Compared with other antidiabetic drugs, pioglitazone was associated with an increased risk of bladder cancer (121.0 v 88.9 per 100 000 person years; hazard ratio 1.63, 95% confidence interval 1.22 to 2.19). Conversely, rosiglitazone was not associated with an increased risk of bladder cancer (86.2 v 88.9 per 100 000 person years; 1.10, 0.83 to 1.47). Duration-response and dose-response relations were observed for pioglitazone but not for rosiglitazone.

Conclusion The results of this large population based study indicate that pioglitazone is associated with an increased risk of bladder cancer. The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect.

Footnotes

  • KBF holds a Canadian Institutes of Health Research new investigator award, and RWP is supported by a Chercheur-National Award of the Fonds de Recherche du Quebec-Santé (FRQS; Quebec Foundation for Health Research).

  • Contributors: MT, KBF, OHY, RWP, and LA conceived and designed the study. LA acquired the data. MT, HY, and LA carried out the statistical analysis. All authors analysed and interpreted the data. MT drafted the manuscript. All authors critically revised the manuscript for important intellectual content. LA obtained funding. LA supervised the study and is the guarantor.

  • Funding: This study is funded by the Canadian Institutes of Health Research.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: this study was funded by the Canadian Institutes of Health Research; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work..

  • Ethical approval: The study protocol was approved by the independent scientific advisory committee of the CPRD (protocol 11_099A) and by the research ethics board of the Jewish General Hospital, Montreal, Canada.

  • Data sharing: No additional data available.

  • Transparency: The lead author (LA) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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